Chapter 9: Biomaterials

Biomaterials can be either naturally occurring (autograft, allograft, or xenograft) or synthetic (alloplastic). Biocompatibility is the term used to describe desirable physicochemical and biologic properties of a material for its intended application rather than the permanence of the implant. There are a number of elements that contribute to biocompatibility including the absence of undesirable effects such as low toxicity, low host reaction, resistance to infection, and physical properties such as easy handling and manipulation. Permanence is an important clinical aspect of an implanted material and is achieved when harmony exists between host and implant. It refers to the long-term biocompatibility between host and implant. Allografts are either living or nonliving tissue derived from the same species donor (e.g., cadaveric skin grafts), whereas autografts are derived from the host (e.g., traditional skin grafts). Xenografts are derived from a different species donor (e.g., bovine/porcine) and include skin substitutes and acellular dermal matrices.

Xenografts are nonliving tissue derived from a different species, i.e., a nonhuman source, most commonly bovine or porcine. They will naturally cause a strong immunologic response with host tissue inflammatory reaction and strong antigenicity, and must be acellular to minimize this. Autografts, not allografts, represent the benchmark to which biomaterials are compared. They do not require processing to reduce their antigenicity because they originate from the host. Although donor site morbidity is not a problem with alloplastic materials, they cause a host reaction such as capsule formation around a breast implant. Allogenic materials include allografts and homografts. Each carries a risk of infectious disease transmission.

Autografts are the benchmark for reconstruction because they are well tolerated by the host and become incorporated into adjacent tissue to provide lifelong reconstruction. However, the disadvantages include the need for a donor site, potential for donor site morbidity, increased surgical time for harvest, and a finite amount of available tissue. An example is the use of alveolar bone graft in cleft lip and palate patients. This can provide permanent bone stock in the alveolus at the expense of temporary donor site morbidity at the hip, which results in a prolonged surgical time and lengthened hospital stay. Hydroxyapatite synthetic material is an alternative substitute that could be used in this setting.

The foreign body reaction is exhibited by all biomaterials and involves a multistaged process involving protein adsorption, fibrinogen deposition, formation of a provisional matrix, recruitment of inflammatory cells, and resolution or formation of a foreign body granuloma. The spectrum of responses includes rejection (e.g., xenograft), fibrous encapsulation (e.g., porous polyethylene or titanium plates), resorption (e.g., suture material breakdown), and incorporation (e.g., acellular matrices and grafts). Therefore, although unhelpful in some situations, the foreign body response is not uniformly so.1,2

ADMs are immunologically inert, but they can mimic cellulitis when used in conjunction with implants or expanders in breast reconstruction. This is termed red breast syndrome.1–3 It does not indicate active infection and therefore does not warrant antibiotic therapy. The manufacturers suggest thorough washing of the product before use because the chemicals and/or preservatives within the ADM are likely responsible for this phenomenon. It is unlikely the patient will need further treatment and will just require reassurance at this time. If she was febrile with a red, hot breast, this would be a different matter and would indicate the presence of an infectious process.

Acellular dermal matrices are nonliving dermal components from an allogenic or xenogenic donor comprised of collagen, elastin, laminin, and glycosaminoglycans. They have a broad range of uses in plastic surgery. A limited number of ADMs are cross-linked and this serves to strengthen the material, prolong its lifespan, and reduce antigenicity. However, this comes at the expense of delayed incorporation, prolonged inflammation, increased infection rate, and bowel adhesion formation. In essence cross-linking tends to make biologic material behave more like a synthetic material.1

The use of an ADM in implant-based breast reconstruction has become a popular option as it is believed to carry a number of potential advantages. First, it provides internal support to the reconstruction, and second, it provides additional thickness of implant coverage. When used with a subpectoral implant placement, it can essentially extend the muscle layer cover in the lower pole where otherwise the implant would only be covered by skin and subcutaneous tissues. When used pre-pectorally, the implant is fully wrapped in ADM and this provides additional cover subcutaneously in both upper and lower poles of the breast. Because the expander/implant is held in place more securely and potentially with less tension, it may enable the surgeon to increase the expander fill or go direct to implant with greater control. There is some evidence that ADM in this setting can reduce the capsular contracture rate. However, the disadvantages include a potential increase in seroma rate and increased total procedural costs.1–3 There has been much debate about the overall benefits of using ADM in breast reconstruction, and an in-depth FDA review in 2019 considered evidence for and against their use. It is currently used off label for this purpose as use is mainly guided by surgeon and patient preference.4,5

AlloDerm is an acellular dermal matrix manufactured from human cadaveric tissue, not a bovine source. It has a minimal host response because it no longer contains antigenic cells. It is well incorporated into tissues, but it can have variable resorption rates. AlloDerm is the most extensively used ADM in the US for breast surgery and has the largest body of evidence in this setting.1 However, it is not licensed for use in the European marketplace and a porcine alternative is offered instead (Strattice). It is also available for off-label use in the US for breast reconstruction according to the FDA.2,3 The FDA classifies human derived and animal derived products differently. This means that a human derived allograft, such as AlloDerm, is classified as a human cell and tissue-based product, while porcine or bovine derived ADMs are medical devices. This impacts the hops through which companies have to pass with product development, and usage differs quite significantly.

Integra is a bilaminar dermal regeneration template used for skin replacement. It consists of a collagen and glycosaminoglycan base with a silicone upper layer that acts as a temporary epidermis. The silicone layer is removed after 3–4 weeks and is replaced with a skin graft. There are a number of ways to assess readiness for autograft when using Integra. One is that the silicone outer layer starts to fray at the edges away from the underlying neodermis. Also, granulation buds become visible at perforating staple or suture sites. In addition, the wound is ready for grafting when it appears a “salmon pink” color. Integra is useful for achieving soft tissue cover over exposed tendon where there is absence of paratenon, or bone without periosteum, as it helps convert a nongraftable wound bed to a graftable one. It is most often used in scar contracture release, venous leg ulcers, pressure ulcers, and burn surgery.1–5

Osteoconduction is the process of surface mediated bone growth, such as from the margin of a graft. Osteoconductive materials are scaffolds (e.g., demineralized bone matrix). Osteogenesis is the overall term used to describe new bone formation. Osteoinduction is the process of recruiting and stimulating osteogenic precursor cells from surrounding tissue into osteoblasts for new bone formation (e.g., bone morphogenic protein). Osseointegration is the direct anchorage of an implant through the formation of a stable bone device (e.g., dental implant, ear prosthesis, or bone anchored hearing device). Currently only bone autografts are osteogenic, i.e., comprised of both cellular and scaffolding components.1–3

Polymethylmethacrylate (PMMA) is a nonresorbable, high-density porous polymer used as a bone cement that also has clinical application in cranial reconstruction, forehead augmentation, and filling gaps in fractures. It is inexpensive, easily molded, inert, biocompatible, and has a high compression strength. However, it involves an exothermic reaction when mixed and can lead to local tissue damage unless adequate tissue cooling is achieved.1,2

Medpor is a high-density polyethylene material available as mesh and various implants, including chin, nasal, malar, and temporal prostheses. Gore-Tex is expanded polytetrafluoroethylene (ePTFE) that is available as mesh, tubes, and blocks. In mesh form it is used for chest and abdominal wall reconstruction; as a solid it is used for facial augmentation.1–3 Marlex is a heavyweight polypropylene mesh that is used in chest and abdominal wall reconstruction.4 Polyether ether ketone (PEEK) is polyether ketone and is a semi-crystalline polymer which has mechanical properties similar to cortical bone. It is resistant to heat and ionizing radiation and is nonferromagnetic which can be useful for postoperative monitoring. Patient-specific implants are becoming increasingly popular especially in craniofacial applications where computed tomography (CT) imaging combined with computer generated three- dimensional modeling can be used to create bespoke custom implants.5 Phasix is an example of a newer absorbable (rather than nonresorbable) polymer used in abdominal wall surgery. It is made from poly-4-hydroxybutyrate (P4HB) and resorbs more slowly than more traditional alternatives such as polylactic acid (e.g., Vicryl, LactoSorb) or polydioxanone (PDS).6

Two-stage flexor tendon reconstruction in the hand involves first reconstructing the flexor sheath and then incorporating new tendon tissue to reconstruct the deficit. By placing a silicone rod (Hunter rod) within the tendon sheath and leaving it in place for a number of weeks, the natural foreign body response is used advantageously. During this time a response to the presence of the silicone rod occurs forming a smooth lined, longitudinal, circumferential capsule around the rod. Then in the second stage when tendon is brought into place, there is a smooth lined pseudo-sheath in place for it. The foreign body response does not negate the need for a tendon autograft, nor accelerate the process of rehabilitation directly. It has no impact on the bacterial load. There needs to be sufficient time between procedures for the pseudo-sheath to form and this is usually around 3 months.1

Breast implant associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon condition which has been noted to occur in patients some years after having breast implants inserted. It is thought to be associated with specific types of textured implants (some of which have now been withdrawn from the market). It develops in the capsule around the implant and patients present with late-onset, peri-implant seromas, rather than an acute-onset red breast which would be more in keeping with infection. Diagnosis is made by sampling the fluid surrounding the implant or from tissue obtained from the capsule. Treatment involves first removing the capsule in its entirety as well as the implant (capsulectomy and explantation), and in most cases this is sufficient treatment. In some cases, further systemic treatment may be warranted. There is no evidence to support the prophylactic removal of implants at a specific time point following their placement. Instead, exchange or removal of implants is generally guided by other factors such as a changing in shape due to capsular contracture or evidence of rupture. Some patients will however elect to have implants changed at a certain time point in the absence of any visible concerns in aesthetics or altered function.1,2

The FDA closely monitors and reports on the evidence in the use of silicone breast implants. Their current recommendation in terms of follow-up is to perform ultrasound for asymptomatic rupture 5–6 years after implantation and every 2–3 years thereafter and magnetic resonance imaging (MRI) for all symptomatic patients. This has changed from previous advice, which was to have regular MRI 3 years after implantation and every 2 years thereafter. FDA approval is present for breast augmentation in patients over 22 years of age and is unrestricted in patients requiring reconstruction. Breast implants may be textured using different techniques including salt loss or foam imprint stamping. Recently, a particular product by Allergan termed “Biocell,” which uses a salt loss technique for texturing, was withdrawn from the market due to concerns over Breast implant associated anaplastic large cell lymphoma (BIA-ALCL). However, the FDA has not advised that all textured implants are withdrawn.1,2

The new breed of composite mesh materials includes Proceed, Sepramesh, Parietex, C-Qur, and TiMesh. These products are mostly used in ventral hernia repairs of the abdominal wall. They can be subdivided into two groups: (1) tissue separating meshes such as Proceed, Sepramesh, and Parietex; (2) coated meshes such as C-Qur and TiMesh. The tissue separating meshes include a nonresorbable polymer on one surface and a biologic or resorbable material on the other side. The porous synthetic is placed against the abdominal wall to encourage host tissue incorporation, while the bioresorbable surface is placed against the viscera to limit bowel adhesions. The polymer is commonly polypropylene and the resorbable material commonly contains cellulose. Coated meshes comprise of a synthetic mesh such as polypropylene coated on both sides with a low inflammatory material such as titanium or omega fatty acids.1–3

Silicone is a nonresorbable polymer based on the element silicon. It has FDA approval as a solid and is most commonly used in breast implant prostheses. Fibrous encapsulation is a consistent finding with silicone implants and this is the basis of capsule formation and subsequent capsular contraction. Fibrous encapsulation can be a useful feature in the context of tissue expansion as the capsule develops a reliable blood supply that can be left in situ under local skin flaps. Silicone is nonporous so it does not facilitate tissue ingrowth in the form of incorporation. However, it is inert so it is not rejected by tissues and is resistant to degradation, thereby having a long lifespan following implantation.1,2